TREFOIL SCAFFOLDING EVOLUTION LIBRARIES

在本申请中，我们建议确定显示的可行性 M13的pIII外壳蛋白上的高度限制的肽基序 丝状噬菌体在成功展示该肽基序后，我们将 开始确定这个基序是否可以进化到结合所需的 通过随机诱变其中一个环中的序列， 这些肽所显示的结构。如果这篇文章中描述的研究 第一阶段的研究是成功的，我们将尝试进一步发展这些 分子通过随机化识别具有更高亲和力的靶标， 后续循环结构。通过这种方式，我们希望创造一种基因 在其上构建非常紧凑和稳定的结合部分， 探索生物学途径并用于临床诊断， 成像、靶向和治疗方案。 拟定商业应用： 小分子的组合文库，可以进化为与 更有利的性质将是非常有价值的工具， 酶和受体的小分子抑制剂或激活剂。这些 分子将被用作研究试剂来探测复杂的 生物过程和临床上它们可以用作诊断， 成像剂、靶向剂或治疗剂。

In this application, we propose to determine the feasibility of displaying a highly constrained peptide motif on the pIII coat protein of M13 filamentous phage. Upon successful display of this peptide motif, we will commence to determine whether this motif can be evolved to bind desired target molecules by randomly mutagenizing the sequences in one of the loop structures displayed by this peptide. If the studies described in this Phase I study are successful we will attempt to further evolve these molecules to recognize the targets with higher affinities by randomizing subsequent loop structures. In this manner, we hope to create a genetic platform on which to build very compact and stable binding moieties for probing biological pathways and utilization in clinical diagnostic, imaging, targeting and therapeutic protocols. PROPOSED COMMERCIAL APPLICATION: Combination libraries of small molecules that can be evolved to bind with more favorable properties will be extremely valuable tools to isolate small molecule inhibitors or activators of enzymes and receptors. These molecules will be utilized as research reagents to probe complex biological processes and clinically they can be used as diagnostic, imaging, targeting, or therapeutic agents.